Background: Studies on the impact of comorbidity and age on postoperative outcome after gastrointestinal tumor resection are scarce. In this study we investigated the impact of comorbidity and age on 30-, 60-, and 90-day mortality after resection of esophageal, gastric, periampullary, colon, and rectal cancer. Methods: The study included 8,583 patients recorded in the population-based Netherlands Cancer Registry, regions Eindhoven (Eindhoven Cancer Registry) and Mid and South Limburg, who underwent resection for cancer stage I-III. Patients were diagnosed between 2005 and 2010. Age was categorized as <65, 65-74, and ≥75 years. Results: Comorbidity was present in more than two-thirds (n = 5,910) of patients. The 30-day mortality rates ranged from 0.5 % for rectal cancer patients <65 years to 12.8 % for gastric cancer patients ≥75 years. Patients with comorbidity who underwent esophageal tumor resection had the highest mortality rates, ranging from 8.4 % for 30-day to 12.0 % for 90-day mortality, while rectal cancer patients had the lowest rates, that is, 4.3-6.4 %, respectively. In multivariable analyses, cardiac disease (odds ratio [OR] = 1.74, 95 % confidence interval [95 % CI] = 1.32-2.30), vascular disease (OR = 1.41, 95 % CI = 1.02-1.95) and previous malignancies (OR = 1.38, 95 % CI = 1.02-1.86) in colon cancer, and cardiac disease (OR = 1.81, 95 % CI = 1.10-2.98) and vascular disease (OR = 1.95, 95 % CI = 1.11-3.42) in rectal cancer were associated with the highest 30-day mortality. Conclusions: Postoperative mortality extends beyond 30 days. Comorbidity and older age are associated with early postoperative mortality after gastrointestinal cancer resection. Underlying comorbidity should be identified preoperatively with attention to patients' specific needs to optimally attenuate risk prior to surgery. A less aggressive treatment approach may well be considered in these groups.